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Institut für Anästhesiologie, Technische Universität München, Klinikum rechts der Isar
(Univ.-Prof. Dr. E. Kochs)
Cerebral blood flow and cerebrovascular response to intermittent hypercapnia during hyperbaric
oxygenation treatment
Marcella Josephine Lanzinger
Vollständiger Abdruck der von der Fakultät für Medizin
der Technischen Universität München zur Erlangung des akademischen Grades eines
Doktors der Medizin
genehmigten Dissertation.
Vorsitzender: Univ.-Prof. Dr. D. Neumeier
Prüfer der Dissertation:
1. apl. Prof. Dr. R. Hipp
2. Univ.-Prof. Dr. G. Tempel
Die Dissertation wurde am 08.01.2002 bei der Technischen Universität München
eingereicht und durch die Fakultät für Medizin am 12.11.2003 angenommen.
2
Table of contents
Introduction .................................................................................................................... 3
Materials and Methods .................................................................................................. 5 Hyperbaric Exposure..................................................................................................... 5 Transcranial Doppler Sonography ................................................................................ 7 Hypercapnia .................................................................................................................. 7 Statistical analysis ......................................................................................................... 8
Results.............................................................................................................................. 8 Biometric data ............................................................................................................... 8 Cardiovascular data ....................................................................................................... 9 Cerebral blood flow velocity....................................................................................... 10 Cerebrovascular reactivity........................................................................................... 11 Complications ............................................................................................................. 12
Discussion ...................................................................................................................... 13 TCD and CBF during HBO......................................................................................... 13 Changes in CBF during HBO ..................................................................................... 13 Relationship of CBF and hyperoxia ............................................................................ 13 Influence of intermittent hypercapnia on time course of CBF.................................... 14 Time course of CBF during HBO ............................................................................... 14 Reversibility of CBF decrease after HBO................................................................... 15 Influence of intermittent hypercapnia on CBF............................................................ 15 Oxygen and carbon dioxide gas tensions during HBO ............................................... 17
Conclusion ..................................................................................................................... 18
Summary ....................................................................................................................... 19
References ..................................................................................................................... 20
Tables and figures......................................................................................................... 24
Abbreviations ................................................................................................................ 25
Dedication...................................................................................................................... 26
3
Cerebral blood flow and cerebrovascular response to intermittent hypercapnia
during hyperbaric oxygenation treatment
Marcella J Lanzinger
Introduction
Hyperbaric oxygenation (HBO) increases tissue oxygen delivery and has several
physiological and pharmacological effects, which include a reduction in cardiac output,
peripheral vasoconstriction, inhibition of β2 – integrin mediated leucocyte adhesion and
lipid peroxidation 14. Experimental data suggest a potential benefit of HBO in
conjunction with head injury and cerebrovascular ischemia and stroke 1,18,22,23, 25,28.
Extremely high blood oxygen tensions (> 1500 mmHg) can be attained during HBO.
The effects of extreme hyperoxia on cerebral blood flow (CBF) have been studied in
animals and to a limited extent in humans 12,19,20,24,26,29. HBO reduces CBF through
arteriolar vasoconstriction, which is caused in part by a decrease in basal arteriolar
vasorelaxation as a result of a decrease in nitric oxide (NO) availability 9,24. However,
the decrease may not be sustained over time. Prolonged HBO exposure at 5 ATA
reveals a cyclic response of CBF in rats with an increase in CBF of up to 50 % above
baseline by 75 min 2,3,8. In head injured patients, the decrease in CBF is also not
consistently sustained over 30 min at pressures up to 2.5 ATA 11,23.
4
Prolonged hypercapnia significantly shortens the period to onset of cerebral convulsions
with HBO. Potential mechanisms include an increase in tissue oxygenation to toxic
levels as a result of cerebral hypercapnic vasodilation, or a worsening of tissue acidosis,
which can develop during HBO as a result of CO2 retention in combination with a lack
of free hemoglobin for venous CO2 transport. However, brief periods of limited
hypercapnia might be able to improve tissue oxygenation as well as CO2 elimination
through intermittent increases in CBF. For the full expression of vasodilation with
hypercapnia under hyperbaric conditions in rats basal NO production is required 7.
Since basal NO is reduced during exposure to HBO cerebral hypercapnic vasodilation
might be impaired and physiological responses of the vasculature to hypercapnia could
differ from those under normobaric, normoxic conditions. Under normal conditions
hypercapnia induced cerebral vasodilation is fully reversible. This may not be the case
during HBO, thereby hastening the onset of central nervous system toxicity through
sustained increases in CBF and oxygenation. In baboons insufflation of 2 % CO2 at 2
ATA caused a normalization of CBF measured by electro-magnetic flowmeter;
Lambertsen proposed a linear relationship between the degree of hypercapnia and
increases in CBF in man, but observations of CBF were abandoned with onset of
symptoms of oxygen toxicity 15,26. In humans during HBO the effect of brief
intermittent CO2 exposure on the cerebral vasculature has not been investigated, and
conclusions based on animal studies are of limited value since effects of HBO may be
species dependent 22.
5
We designed our study to evaluate CBF under the conditions of a routinely used HBO
treatment profile, with healthy volunteers breathing 100% O2 at 2.5 ATA for 70 min, to
determine:
1) if there is a continuous decrease in CBF with increasing oxygen tension,
2) if the decrease in CBF at maximum pressure is sustained, and
3) if the cerebral vasculature maintains a dynamic response to hypercapnia.
Materials and Methods
After institutional review board approval and informed consent, 29 adult volunteers (8
female, 21 male, ages 20 – 53) were included in the study. Procedures followed were in
accordance with institutional guidelines. Individuals with the following criteria were
excluded: medication affecting vascular reactivity including nitrates, beta-blockers and
calcium channel antagonists, a history of cardiac disease, a history of cerebral events
including seizure and stroke, pulmonary disease, pregnancy, claustrophobia, or inability
to autoinflate the middle ear. Subjects were assigned to one of two groups, group HBAir
or group HBOx. Each subject was studied one time only. Throughout the study heart
rate and non-invasive blood pressure were monitored and recorded (Sirecust 630,
Siemens, Germany). A physician was immediately present to monitor for complications
during hyperbaric exposure.
Hyperbaric Exposure
6
All studies were performed in a multiplace hyperbaric chamber (Medstar 2000, Fa.
HAUX, Germany). Subjects were exposed to this HBO protocol: Compression over 15
min to a maximum pressure of 2.5 ATA (equals 15 meters of sea water) for 70 min
followed by decompression at a rate of 0.1 ATA/min. Subjects were comfortably seated
breathing room air (group HBAir) or 100% oxygen via a tightly fitting Scott mask
(group HBOx). Room air oxygen content was monitored to detect incomplete mask seal
indicating less than 100% oxygen inhalation. During decompression all subjects
breathed oxygen to minimize risk for decompression illness. After decompression all
subjects breathed room air. The exposure pattern for the two groups is displayed in
figure 1.
Figure 1. Exposure pattern for group HBOx and group HBAir.
Baseline measurements at 1.0 ATA room air followed by compression at 0.1 ATA per
minute to 2.5 ATA, 70 min at 2.5 ATA, decompression at 0.1 ATA per minute, follow-
up for 10 min. Group HBOx breathing 100% oxygen until end of hyperbaric exposure,
group HBAir breathing room air throughout, except during decompression.
Cerebrovascular reactivity testing at seven timepoints by closed circuit rebreathing over
1.01.52.02.5
0 15 45 75 85
ATA
time (min)
oxygenroomair
HBOxHBAir
100 110
Rebreathe x x x x x x x
7
10 respirations: 1.5 ATA, 2.0 ATA, 2.5 ATA/0 min, 2.5 ATA/30min, 2.5 ATA/60 min,
1.0 ATA/0 min, 1.0 ATA/10 min.
Transcranial Doppler Sonography
TCD was performed continuously throughout the study. Mean arterial blood flow
velocity (Vmean) was measured in the proximal M1 segment of the middle cerebral artery
(MCA) 31. After manual localization of the optimal signal a 2 MHz TCD probe
(MultiDop, DWL, Esslingen, Germany) was securely attached using a headband. Visual
and acoustic signals were monitored continuously for optimal signal transduction by an
investigator inside the chamber. Data were digitized and recorded on a hard drive for
analysis.
Hypercapnia
Cerebrovascular response to hypercapnia was evaluated in five subjects in group HBAir
and 15 subjects in group HBOx at seven time points during hyperbaric exposure: 1.5
ATA, 2.0 ATA, 2.5 ATA at 0 min, 2.5 ATA at 30 min, 2.5 ATA at 60 min, 1.0 ATA at
0 min (group HBOx only), 1.0 ATA at 10 min (group HBOx only). Hypercapnia was
induced at each time point by rebreathing for 10 respirations into a closed circuit with
an approximate volume of 3.4 l.
Experiments at 1.0 ATA had demonstrated a 15 mmHg rise in end-tidal CO2 after 10
respirations via the closed circuit. The factors that determine the rise in CO2 are the
8
volume of deadspace and the amount of CO2 in the expired gas. The same closed circuit
set-up was used for all subjects who rebreathed for 10 respirations without consciously
changing their respiratory rate. The amount of CO2 in the expired gas is determined by
the CO2 production of the subject. Resting CO2 production rate has been shown to be
independent of ambient pressure or inspired PO2 up to 3.06 ATA 5,30. Therefore, the rise
in CO2 with rebreathing can be expected to be similar under hyperbaric conditions.
Statistical analysis
Data were analyzed in a mixed model. Evaluation for normality was by Shapiro-Wilk
test. Two-sided Wilcoxon two-sample rank-sum test was used for differences between
groups at each time point; paired t-test with Bonferroni correction for comparison
against baseline values. P < 0.05 was considered statistically significant for single
comparisons.
Results
Biometric data
Biometric data with baseline blood pressures and heart rate are displayed in table 1.
There were no differences between groups except for baseline heart rate, which was
higher in group HBOx, P = 0.03. Vmean at any time point was determined by analysis of
digitized data as the mean blood flow velocity over five heart beats.
9
Table 1. Baseline biometric and physiological data
group HBAir HBOx
age years 38.0 ± 6.5 39.3 ± 9.9
height cm 178.0 ± 7.9 176.3 ± 8.8
weight kg 79.0 ± 11.3 73.2 ± 12.3
heart rate min-1 71.2 ± 7.9 78.8 ± 8.9*
SBP mmHg 139.6 ± 21.1 137.8 ± 23.5
DBP mmHg 86.2 ± 16.4 81.6 ± 15.4
MAP mmHg 103.3 ± 17.3 100.3 ± 17.3
Vmean mm s-1 514 ± 121 584 ± 101
male/female 12/2 9/6
DBP = diastolic blood pressure, MAP = mean arterial blood pressure, SBP = systolic
blood pressure, Vmean = mean cerebral blood flow velocity in the middle cerebral artery
Data are given as mean ± standard deviation. * P = 0.03 HBOx vs HBAir
Cardiovascular data
Heart rate decreased significantly during hyperbaric exposure reaching a minimum at
2.5 ATA / 30 min, 63.3 ± 7.2 min-1 in group HBAir, P < 0.001, and 62.0 ± 8.3 min-1 in
group HBOx, P < 0.001 vs baseline. There were no differences between groups over
time (table 2). Blood pressures did not differ significantly between groups. Mean
arterial and diastolic blood pressure increased over time in group HBOx, P = 0.016 and
10
P = 0.006. Systolic blood pressure did not change over time. There was no gender
influence on heart rate or blood pressures.
Table 2. Heart rate and mean arterial blood pressure over time
group 1.5 ATA 2.0 ATA 2.5 ATA 0 min
2.5 ATA 30 min
2.5 ATA 60 min
1 ATA
HR HBAir 68.6 ± 7 66.7 ± 7 63.8 ± 7 63.3 ± 7* 64.1 ± 10 66.7 ± 10
HBOx 73.3 ± 10 69.1 ± 9 65.3 ± 10 62.0 ± 8 63.8 ± 8 65.9 ± 10
MAP HBAir 102.8 ± 17 102.4 ± 14 99.5 ± 16 106.1 ± 17 104.5 ± 22 101.9 ± 19
HBOx 98.1 ± 19 96.0 ± 16 99.1 ± 18 99.2 ± 16 97.4 ± 12 102.8 ± 18
HR = heart rate in beats per minute, MAP is mean arterial blood pressure in mmHg
Data are shown as mean ± standard deviation. *P = 0.03 group HBOx vs group HBAir
Cerebral blood flow velocity
Data for Vmean are shown in figure 2. To eliminate inter-individual differences of
absolute blood flow velocities as a result of differences in vessel diameter and
insonating angle, Vmean is presented as percent of baseline values. The maximal decrease
in Vmean occurred in group HBOx on compression to 2.5 ATA with a mean reduction of
19%, P < 0.001 vs baseline.
11
Figure 2. Continuous Vmean during HBO over time.
expressed as a percentage of baseline Vmean (mean±SD). Eight time points are displayed
by pressure, with three time points at 2.5 ATA, representing 0 min, 30 min, and 60 min
exposure, and three time points at 1 ATA representing baseline, end of exposure, and 10
min after end of exposure. Mean change in Vmean was significantly different between
groups at pressure, P < 0.0002. In group HBAir Vmean decreased at 2.5 ATA / 0 min by 4
%, P = 0.05 vs baseline; the decrease seen after decompression is a result of breathing 100
% during this period. In group HBOx Vmean decreased significantly by 17 % at 1.5 ATA, P
< 0.0001 vs baseline, with a maximal decrease of 19 % at 2.5 ATA / 0 min, P = 0.15 vs
1.5 ATA. Vmean at 2.5 ATA / 30 min was slightly less decreased with 16 %, P = 0.05 vs
2.5 ATA / 0 min. Vmean in group HBOx returned to baseline 10 min after end of treatment.
Cerebrovascular reactivity
Cerebrovascular reactivity to hypercapnia, calculated as maximal increase in Vmean after
rebreathing as a fraction of Vmean before the test, was unchanged over time in both
groups while at pressure, with a trend towards a less pronounced response in group
HBOx, P = 0.02 at 2.5 ATA/30 min vs group HBAir (figure 3). After decompression
707580859095100105
1.0 1.5 2.0 2.50'
2.530'
2.560'
1.00'
1.010'
ATA
Vm
ean % HBOx
HBAir
oxygenroomair
HBOxHBAir
12
cerebrovascular reactivity to hypercapnia was significantly reduced in group HBOx, P =
0.002. In group HBAir evaluation of the hypercapnic response was limited to five
subjects with 24 measurements performed satisfactorily. In group HBOx 15 subjects
were studied with 88 satisfactory measurements. There was no influence of gender.
There was no significant difference in Vmean before and after hypercapnia at each time
point.
Figure 3. Cerebrovascular reactivity with hypercapnia
Data are shown as mean + SD for each time point. *P = 0.02 group HBOx vs. group
HBAir at 2.5 ATA / 30 min; †P = 0.002 group HBOx at pressure vs. 1 ATA after
decompression.
Complications
There were no complications in any of our subjects due to hyperbaric exposure,
hyperbaric oxygenation, or hypercapnia.
01020304050607080
1.5 2.0 2.5 2.530'
2.560'
1.00'
1.010'
ATA
% in
crea
se V
mea
n HBAirHBOx
oxygenair
HBOxHBAir
0'
† †*
13
Discussion
TCD and CBF during HBO
Vmean is decreased by 19% during an HBO protocol of 70 min at 2.5 ATA. This
represents an equivalent decrease in CBF if the assumption is correct that the diameter
of the blood vessel in which flow velocities were measured did not change 4.
Angiographic studies at 2.4 ATA demonstrated no appreciable change in the diameter
of large or medium sized cerebral vessels in dogs breathing 100% oxygen 10. This
included the MCA, which we targeted in our measurements. We therefore suggest that
even under the influence of extreme hyperoxia changes in Vmean of the MCA reflect
changes in CBF.
Changes in CBF during HBO
The magnitude of decrease in CBF demonstrated in our study is consistent with the
results of previous studies. Kety and Schmidt in 1948 first demonstrated a 13% decrease
in CBF in response to breathing 100% oxygen at 1 ATA, Lambertsen measured a 25%
decrease at 3.5 ATA, and Ohta an 18% decrease at 3 ATA 13,16,19. Demchenko studied
regional CBF in rats and after 30 min of HBO found a maximal decrease of 26 – 39 %
at 3 ATA 8.
Relationship of CBF and hyperoxia
14
We measured a continuous decrease in CBF up to our maximum pressure (2.5 ATA).
This does not support findings in human volunteers which suggested the trend of a
lesser decrease in CBF when breathing 100% oxygen at pressures higher than 2 ATA 19.
However, our results are consistent with findings by Demchenko who in rats
demonstrated a continuous decrease in regional CBF during HBO with increasing
barometric pressure which was maximal at 3 ATA 8. In our study, beyond 1.5 ATA with
a 17% decrease in CBF, additional decreases were observed though not statistically
significant, but this may have been due to insufficient numbers in our study to reach
statistical significance. We did not see an increase in CBF during compression to 2.5
ATA.
Influence of intermittent hypercapnia on time course of CBF
Intermittent hypercapnia might have influenced the changes in CBF. However, there
was no significant difference in Vmean values before and immediately after rebreathing,
and we conclude the influence of intermittent hypercapnia on the overall time course of
CBF to be negligible.
Time course of CBF during HBO
Experimental data on rats have demonstrated that the decrease in CBF during HBO at
high pressures is not sustained over time 3,8. After 30 min of HBO at 5 ATA CBF
increased and reached pre-exposure levels within 60 min increasing up to 50 % in
addition within 75 min; at pressures less than 5 ATA the decrease in CBF was sustained
15
over 75 min 8. During our HBO exposures we demonstrated only a slight relative
increase in CBF after 30 min at 2.5 ATA which resolved within the next 30 min
resulting in no overall change for the exposure period of 70 min at 2.5 ATA. We
exposed our subjects to HBO over a time period within which a secondary increase in
CBF has been shown to occur, but we did not expose them to the same maximum
pressure. Therefore the degree of hyperoxia in our study was less pronounced, which
might explain why we did not observe the increase in CBF that has been reported at
higher pressures. The slight increase which we noted could be interesting, however,
given the inherent limitations of TCD measurements and estimation of CBF, we do not
believe that any conclusions should be based on this observation.
Reversibility of CBF decrease after HBO
All of our subjects experienced a full recovery of CBF to pre-exposure values within 10
min of return to breathing room air at 1 ATA. There was no rebound phenomenon as
seen in rats at 5 ATA HBO with reversal of cerebral vasoconstriction or as suggested in
a study on severely brain injured patients after 1 hour at 1.5 ATA 8,23. Our results
suggest that the decrease in CBF as measured by TCD is reversible within a short time
after cessation of HBO after 70 min at 2.5 ATA and appears to be limited to this period.
Influence of intermittent hypercapnia on CBF
The increase in CBF during HBO following inhalation of CO2 is a recognized
phenomenon 14. However, in humans direct measurements on the extent and course of
16
the response are limited. Lambertsen performed measurements of the cerebral arterio-
venous oxygen difference in four male patients during inhalation of 2 % CO2 in oxygen
at 3.5 ATA. He measured a 58 % decrease in the arterio-venous oxygen difference
compared to 100 % oxygen inhalation at 3.5 ATA, which he deducted to be the result of
increased oxygen delivery through increased cerebral blood flow 15. We observed a
mean CBF increase by more than 30% in response to hypercapnia during HBO at 2.5
ATA for 70 min, which was consistent within each individual subject over time. The
response was less pronounced compared to room air breathing at 2.5 ATA (group
HBAir vs group HBOx, P = 0.02 at 2.5 ATA / 30 min); this is similar to the findings in
rats at 4 ATA and is possibly related to lack of available NO during HBO for full
expression of the hypercapnic vasodilatory response in the brain 6. However, the
increase in CBF with hypercapnia was not prolonged and CBF returned to pre-test
values briefly after termination of closed circuit rebreathing. No adverse effects were
noted in any of our subjects due to temporary increases in CBF with hypercapnia. Our
results indicate that during HBO the cerebral circulation remains dynamic and is able to
respond to a CO2 challenge with vasodilation during the hypercapnic period and that this
effect is reversible with reestablishment of normocapnia.
After HBO increases in CBF in response to hypercapnia were still reduced. Following
reversal of cerebral vasoconstriction this seems to indicate a limited ability for
vasodilatory response in the cerebral vasculature after HBO. A similar situation has
recently been demonstrated in conjunction with cerebral vasodilation secondary to
hemodilution 27. These observations are consistent with the mechanism of
vasorelaxation mediated by NO, and a limited availability of NO as a result of HBO 9,24.
17
Normal values for CO2-reactivity testing under normobaric conditions are variable
depending on the technique, ranging from 10 to 24 % change in Vmean per 1 vol%
change in CO2 31. We measured a 30 % increase in Vmean for a 15 mmHg rise in PetCO2.
Despite the obvious limitations of this comparison it indicates that cerebrovascular
reactivity to hypercapnia during HBO at 2.5 ATA demonstrates the same order of
magnitude as under normobaric, normoxic conditions.
Oxygen and carbon dioxide gas tensions during HBO
We did not ascertain changes in arterial O2 or CO2 (PaO2 or PaCO2) by direct
measurement. However, the effects of HBO on blood gases are well known 17. At 2.5
ATA breathing 100% oxygen the alveolar oxygen tension (PAO2) is calculated to 1813
mmHg 21. PaO2 would be slightly lower than predicted due to physiologic shunting and
the dilution of PAO2 with nitrogen diffusing out of tissues 5,21. PaCO2 during HBO under
resting conditions is not significantly different from 1 ATA 5,30. By using a standardized
rebreathing technique a very similar degree of hypercapnia was produced in all subjects
allowing a comparison of subjects within our study. Variations between subjects could
occur due to a difference in lung volumes since the volume of the closed circuit was
fixed. Smaller tidal volume would be associated with a lesser degree of rebreathing.
Basing tidal volume on body weight (HBAir 79, 62 – 99 kg; HBOx 73, 53 – 98 kg,
mean, min-max) shows a similar distribution in both groups so that we believe the
influence of inter-individual differences in deadspace volume on the degree of
hypercapnia to be minimal. Therefore, the degree of hypercapnia induced using the
18
rebreathing technique described earlier should be consistent under the conditions in this
study (1.0 -2.5 ATA).
Conclusion
We evaluated the effects of a routinely used HBO treatment protocol and intermittent
hypercapnia on the cerebral vasculature using TCD. HBO with 100% oxygen causes a
sustained decrease in CBF at 2.5 ATA over 70 min, which is reversed within 10 min
after end of exposure. Cerebral vasodilation in response to intermittent hypercapnia is
slightly less pronounced compared to room air breathing and the effects reversible with
reestablishment of normocapnia.
19
Summary
Background and purpose: The decrease in cerebral blood flow (CBF) through cerebral
vasoconstriction caused by extreme hyperoxia could promote the onset of central
nervous system oxygen toxicity during hyperbaric oxygenation (HBO). CBF increases
with hypercapnia, but the effects of intermittent hypercapnia during HBO exposure on
CBF have not been determined. The aim of the study is to evaluate CBF and
cerebrovascular reactivity to hypercapnia during HBO at 2.5 atmospheres absolute
(ATA) for 70 min using transcranial doppler sonography (TCD) in healthy volunteers.
Methods: 29 adult subjects were studied during a routine compression profile: 2.5 ATA
for 70 min. Fifteen subjects received 100% oxygen simulating a HBO treatment, 14
subjects breathed room air. TCD with a 2 MHz probe was used to continuously measure
mean blood flow velocities (Vmean) in the middle cerebral artery. Cerebrovascular
reactivity was assessed by response to hypercapnia induced by standardized rebreathing.
Results: Vmean decreased by 19% during HBO at 2.5 ATA for 70 min, P<0.0001, and
returned to baseline within 10 min after end of exposure. Hyperbaric exposure alone did
not change Vmean. Heart rate and blood pressure did not differ between groups over time.
Hypercapnic cerebral vasodilation tended to be less pronounced in the HBO group,
P=0.02 after 30 min at 2.5 ATA, but reversible with termination of hypercapnia.
Conclusions: HBO at 2.5 ATA for 70 minutes causes a sustained decrease in CBF,
which is reversible within 10 min after end of exposure. Cerebral hypercapnic
vasodilation is slightly reduced during HBO and reversible with normocapnia.
20
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24
Tables and figures
Figure 1. Exposure pattern for group HBOx and group HBAir. ...................................... 6
Table 1. Baseline biometric and physiological data ......................................................... 9
Table 2. Heart rate and mean arterial blood pressure over time..................................... 10
Figure 2. Continuous Vmean during HBO over time. ...................................................... 11
Figure 3. Cerebrovascular reactivity with hypercapnia.................................................. 12
25
Abbreviations
ATA atmospheres absolute
CBF cerebral blood flow
CO2 carbon dioxide
DBP diastolic blood pressure
HBO hyperbaric oxygenation
HR heart rate
MAP mean arterial pressure
MCA middle cerebral artery
NO nitric oxide
O2 oxygen
PaCO2 arterial carbon dioxide gas tension
PACO2 alveolar carbon dioxide gas tension
PaO2 arterial oxygen gas tension
PAO2 alveolar oxygen gas tension
SBP systolic blood pressure
TCD transcranial doppler sonography
Vmean mean arterial blood flow velocity in the middle
cerebral artery
26
Dedication
This thesis is dedicated to my parents in gratitude and acknowledgement of their
continued unfailing love and support. Thank you.